The present invention relates to a process for preparing optically-active cyanohydrins by enzymatic reaction of oxo compounds with hydrocyanic acid in the presence of (R)- or (S)-oxynitrilase (4.1.2.10) or (4.1.2.11), respectively, under conditions sufficiently acid for the competing chemical reaction which produces racemates to be negligible.
Optically-active cyanohydrins are of considerable interest for obtaining optically-active .alpha.-amino alcohols, .alpha.-hydroxy carboxylic acids, heterocycles and pyrethroid insecticides. Of central importance in this connection is the availability of chiral synthons that can be easily derivatized and that can be prepared at reasonable cost in adequate amounts with maximum enantiomer excess (ee).
In view of the optical selectivity of enzymatic reactions, the enzyme-catalyzed preparation of optically-active cyanohydrins has already been investigated. The optical purity of these compounds is a function of the efficiency of suppression of the competing chemical reaction.
German Patent 1,300,111 describes the preparation of optically-active cyanohydrins using (R)-oxynitrilase bound to ion exchangers at pH 5.4. However, the ee values achieved in the process were all below 90%.
Effenberger et al. (Anoew. Chem. 99:49 (1987)) therefore recommended the enzymatic reaction of oxo compounds with hydrocyanic acid in organic water-immiscible solvents in order to suppress the chemical reaction. A preferred process used enzyme immobilized on a support in ethyl acetate at pH values of 5.4. The ee values achieved were up to 99%. However, enzyme stability is lower in organic media.
Another way of suppressing the competing chemical reaction and racemization is disclosed in EP 326 063. According to this reference optically-active cyanohydrins are said to be obtained by reacting oxo compounds with hydrocyanic acid in the presence of oxynitrilase under conditions sufficiently acid, especially at pH values less than or equal to 4.5, and at such temperatures that the competing chemical reaction and racemization are negligible compared with the enzymatic synthesis. A low pH causes low enzyme activity. Increased losses in activity of the biocatalyst under these conditions are reported, and the examples reveal that low temperatures in the range from 5.degree. to 8.degree. C. are favored.